scholarly journals Efficacy and tolerability of the investigational topical cream SD-101 (6% allantoin) in patients with epidermolysis bullosa: a phase 3, randomized, double-blind, vehicle-controlled trial (ESSENCE study)

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Amy S. Paller ◽  
◽  
John Browning ◽  
Milos Nikolic ◽  
Christine Bodemer ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Wound Closure ◽  
Trial Registration ◽  
Controlled Study ◽  
Phase 3 ◽  
Double Blind ◽  
Treatment Groups ◽  
Topical Cream ◽  
Link Type ◽  
Total Body

Abstract Background Epidermolysis bullosa (EB) is a rare genetic disorder that manifests as blistering and/or skin erosion. There is no approved treatment for EB; current standard of care consists of wound and pain management. SD-101 6% is a topical cream containing 6% allantoin that was developed for treating skin lesions in patients with EB. The aim of this phase 3, multicenter, randomized, double-blind, vehicle-controlled study was to assess the efficacy and safety of SD-101 6% cream versus vehicle (0% allantoin) on lesions in patients with EB. Methods Eligible patients were ≥1 month old, had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10–50 cm2 in size that was present for ≥21 days. Patients were randomly assigned to SD-101 6% cream or vehicle, which was applied topically once a day to the entire body for 3 months. Primary efficacy endpoints were time to complete target wound closure within 3 months and the proportion of patients who experienced complete target wound closure within 3 months. Post hoc subgroup analyses were conducted by patient age and in those with body surface area index of total body wound burden ≥5% at baseline. Results In total, 169 patients were enrolled and randomly assigned to SD-101 6% (n = 82) or vehicle (n = 87). Baseline demographics and disease characteristics were similar between treatment groups. There were no statistically significant differences between treatment groups in time to target wound closure (hazard ratio, 1.004; 95% confidence interval [CI] 0.651, 1.549; P = 0.985) or proportion of patients with complete target wound closure within 3 months (odds ratio [95% CI], 0.733 [0.365, 1.474]; nominal P = 0.390). A positive trend toward faster wound closure with SD-101 6% versus vehicle was observed in patients aged 2 to <12 years and those with total body wound burden ≥5% at baseline. SD-101 6% cream was well tolerated. Conclusions SD-101 6% cream for treatment of EB-associated lesions was not more effective than vehicle in shortening the time to complete target wound closure or achieving complete target wound closure within 3 months. Trial registration ClinicalTrials.gov, NCT02384460; Date of trial registration, February 13, 2015; First participant enrolled, March 11, 2015.

scholarly journals Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e047993
Author(s):  
Nirosen Vijiaratnam ◽  
Christine Girges ◽  
Grace Auld ◽  
Marisa Chau ◽  
Kate Maclagan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Primary Outcome ◽  
Phase 3 ◽  
Double Blind ◽  
Treatment Groups ◽  
Link Type ◽  
South Central ◽  
Disease Modifying ◽  
Secondary Outcomes

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.

scholarly journals EXPRESS: Efficacy and Safety of Tadalafil in a Pediatric Population with Pulmonary Arterial Hypertension: Phase 3 randomized, Double Blind Placebo-Controlled Study

2021 ◽  
pp. 204589402110249
Author(s):  
David D Ivy ◽  
Damien Bonnet ◽  
Rolf MF Berger ◽  
Gisela Meyer ◽  
Simin Baygani ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Statistical Significance ◽  
Significance Testing ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Statistical Significance Testing ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Treatment Groups ◽  
Pulmonary Arterial

Objective: This study evaluated the efficacy and safety of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH). Methods: This phase-3, international, randomized, multicenter (24 weeks double-blind placebo controlled period; 2-year, open-labelled extension period), add-on (patient’s current endothelin receptor antagonist therapy) study included pediatric patients aged <18 years with PAH. Patients received tadalafil 20 mg or 40 mg based on their weight (Heavy-weight: ≥40 kg; Middle-weight: ≥25—<40 kg) or placebo orally QD for 24 weeks. Primary endpoint was change from baseline in 6-minute walk (6MW) distance in patients aged ≥6 years at Week 24. Sample size was amended from 134 to ≥34 patients, due to serious recruitment challenges. Therefore, statistical significance testing was not performed between treatment groups. Results: Patient demographics and baseline characteristics (N=35; tadalafil=17; placebo=18) were comparable between treatment groups; median age was 14.2 years (6.2 to 17.9 years) and majority (71.4%, n=25) of patients were in HW cohort. Least square mean (SE) changes from baseline in 6MW distance at Week 24 was numerically greater with tadalafil versus placebo (60.48 [20.41] vs 36.60 [20.78] meters; placebo-adjusted mean difference [SD] 23.88 [29.11]). Safety of tadalafil treatment was as expected without any new safety concerns. During study period 1, two patients (1 in each group) discontinued due to investigator’s reported clinical worsening, and no deaths were reported. Conclusions: The statistical significance testing was not performed between the treatment groups due to low sample size, however, the study results show positive trend in improvement in non invasive measurements, commonly utilized by clinicians to evaluate the disease status for children with PAH. Safety of tadalafil treatment was as expected without any new safety signals.

scholarly journals Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

2021 ◽  
Author(s):  
Ravi Savarirayan ◽  
Louise Tofts ◽  
Melita Irving ◽  
William R. Wilcox ◽  
Carlos A. Bacino ◽  
...  
Keyword(s):  
Growth Velocity ◽  
Bone Growth ◽  
Growth Factor Receptor ◽  
Extension Study ◽  
Controlled Study ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Pathogenic Variants ◽  
Growth Promoting

Abstract Purpose Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

scholarly journals POS-380 A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ATRASENTAN IN PATIENTS WITH IGA NEPHROPATHY (THE ALIGN STUDY)

2021 ◽  
Vol 6 (4) ◽  
pp. S164-S165
Author(s):  
H. Lambers Heerspink ◽  
D. Kohan ◽  
R. Lafayette ◽  
A. Levin ◽  
H. Zhang ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Controlled Study ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

Results of the phase 1b soft-tissue sarcoma (STS) portion of the global randomized, double-blind, placebo-controlled study of tazemetostat (TAZ) plus doxorubicin (DOX) as frontline therapy for advanced epithelioid sarcoma (ES).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11563-11563
Author(s):  
Sant P. Chawla ◽  
Gerald Steven Falchook ◽  
Melissa Amber Burgess ◽  
James Lin Chen ◽  
Robin Lewis Jones ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Safety Profile ◽  
Controlled Study ◽  
Pharmacokinetic Data ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Limited Effectiveness ◽  
Phase 1B ◽  
Frontline Therapy

11563 Background: ES is a rare, aggressive subtype of STS for which cytotoxic chemotherapy has limited effectiveness. TAZ, an FDA-approved EZH2 inhibitor, has shown single-agent clinical activity and a favorable safety profile in patients with metastatic or locally advanced ES. In preclinical studies, TAZ has shown synergistic antitumor activity with DOX, which is often used as frontline treatment for STS. Here, we present results of the phase 1b study (NCT04204941), designed to assess the recommended phase 3 dose (RP3D), safety, and efficacy of TAZ + DOX in patients with advanced STS. Methods: The open-label, phase 1b portion of this study enrolled adult patients with previously untreated advanced STS. A standard 3 + 3 design was used to assess TAZ 400 mg, 600 mg, and 800 mg orally twice daily in combination with DOX (75 mg/m2 intravenously on day 1 of each cycle, for up to 6 cycles) as frontline therapy. Dose-limiting toxicities (DLTs) were predefined in the protocol. The RP3D of TAZ was determined by Scientific Review Committee review of the safety and pharmacokinetic data from the phase 1b trial, with a target DLT rate of < 33%. Results: As of February 1, 2021, 16 patients are enrolled, including 2 with ES; 10 are still receiving TAZ + DOX and 6 have discontinued (5 due to disease progression, 1 due to patient withdrawal). The median age was 49.5 years (range, 29–82) and all had unresectable STS. Median (range) time on treatment was 13 (0.1–51.1+) weeks across all dose levels evaluated. Two DLTs, both of febrile neutropenia, were observed, one in the TAZ 600 mg + DOX cohort (n = 1/6, 17%), and one in the TAZ 800 mg + DOX cohort (n = 1/3, 33%). When used in combination with DOX, the RP3D of TAZ was 800 mg. Grade 3 or 4 treatment-related treatment-emergent adverse events (TR-TEAEs) occurred in 13/16 (81.3%) patients. The most common (≥ 20%) TR-TEAEs were neutropenia (n = 11, 69%), anemia (n = 10, 63%), fatigue (n = 10, 63%), stomatitis (n = 9, 56%), nausea (n = 8, 50%), febrile neutropenia (n = 7, 44%), constipation (n = 6, 38%), vomiting (n = 6, 38%), and decreased appetite (n = 5, 31%). TR-TEAEs were defined as attributable to either study agent. Conclusions: The combination of TAZ + DOX was generally well tolerated in this dose finding study in patients with advanced STS. The RP3D to be tested in the phase 3 randomized, double blind, placebo controlled study is TAZ 800 mg twice daily + DOX. The safety profile of this combination is consistent with the respective safety information for TAZ and for DOX. The TR-TEAEs include known toxicities of DOX or TAZ. Further comparison with DOX + placebo in the phase 3 trial will aid in assessing efficacy and safety of the combination of TAZ + DOX. The global phase 3 confirmatory trial will enroll patients with ES who have unresectable disease and have had no prior systemic therapy. Clinical trial information: NCT04204941.

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